A base pair resolution map of nucleosome positions in yeast

The exact positions of nucleosomes along genomic DNA can influence many aspects of chromosome function, yet existing methods for mapping nucleosomes do not provide the necessary single base pair accuracy to determine these positions. Here we develop and apply a new approach for direct mapping of nucleosome centers based on chemical modification of engineered histones. The resulting map locates nucleosome positions genome-wide in unprecedented detail and accuracy. It reveals novel aspects of the in vivo nucleosome organization that are linked to transcription factor binding, RNA polymerase pausing, and the higher order structure of the chromatin fiber. Nucleosomes distort and occlude the genomic DNA from access to most DNA-binding proteins, and their exact positions affect the structure of the chromatin fiber1. Even single base pair shifts of the position of a nucleosome can change chromatin configurations2 and protein binding kinetics3, 4, 5. A single base pair resolution map of nucleosome positions is necessary to fully understand a wide range of biological processes including RNA polymerase activity6, 7, 8, transcription factor binding kinetics4, 5, 9, 10, DN